Rob Thomas Profile:

1. Rob Thomas Profile: • 20 year old college student • Type 1 diabetes, uses combination of rapid onset & long acting insulin • To celebrate victory of interfaculty soccer competition, went on a “pub crawl” • Developed signs and symptoms suggestive of hypoglycaemia

2. ACUTE DIABETES CASE STUDY F • Thi - what is hypoglycaemia ? what precipitated Rob’s condition ? • Tu - what other factors associates with hypo? what are the treatments for hypo ? • Tuan - what form/formulation is glucagon available ?

3. What is hypoglycaemia? • Also called low blood sugar, occurs when blood sugar level drops too low to provide enough energy for body's activities • Hypoglycaemia, a common emergency complication that can happen in diabetes • Side effect of diabetes treatment • Also result from other medications or diseases, hormone or enzyme deficiencies, or tumors

4. ……continued • When blood glucose falls • Glucagon signals liver to break down glycogen & release glucose • Raising the blood glucose level towards normal • In diabetes • Glucagon response to hypoglycemia may be impaired • Making it harder for glucose level to return to normal

5. Normal & target blood glucose ranges • Normal fasting plasma glucose range is between • 3.6 – 5.8 mmol/L • Hypoglycaemia occurs when plasma glucose levels are below • 2.2 – 2.5 mmol/L

6. Symptoms of hypoglycaemia • Varies from person to person • hunger • nervousness & shakiness • perspiration • dizziness or light-headedness • confusion • difficulty speaking • feeling anxious or weak • Severe hypoglycaemia can cause unconsciousness

7. ……continued • Hypoglycaemia can also happen while sleeping • cry out or have nightmares • pajamas or sheets are damp from perspiration • feel tired, irritable, or confused when wake up

8. Causes of hypoglycaemia • Blood glucose can fall for a number of reasons: • meals or snacks that are too small, delayed, or skipped • excessive doses of insulin • increased activity or exercise • excessive drinking of alcohol

9. What precipitated Rob’s hypoglycaemia? • Alcohol leading to hypo • Alcohol potentiate the actions of insulin & oral hypoglycaemic medications • Prevents liver from producing glucose, even one to two days after drinking • Binge drinking or drinking on a empty stomach, can interfere with release of glycogen from the liver to the bloodstream

10. ……Rob’s hypoglycaemia • Alcohol related hypoglycaemia can be dangerous because, signs/symptoms can be mistaken for drunkenness • Unconsciousness • Seizures • Slurred speech • Blurred vision

11. ……Rob’s hypoglycaemia • Therefore, Rob’s hypoglycaemia is precipitated by the alcohol consumed on the “pub crawl” • Hypoglycemia caused by excessive drinking can be very serious & even fatal • Should be taken in moderation & with care especially Type 1 diabetics (suggest limit of max 2 drinks/day)

12. What other factors are associated with hypoglycaemia? • Drugs • high dose salicylates (potentiate the action of insulin) • MAOI • Anabolic steroids • Some antibacterials • Some antifungals

13. ……continued • Hypoglycaemia result possibly due to: • competition for the metabolising enzyme • interference with plasma protein binding • interference with excretion of anti-diabetic agent

14. ……continued • Other drugs do not necessarily affect BSL but masks the symptoms of hypoglycaemia such as: B - Blockers!!!!! • Prefer B1 - selective e.g. atenolol

15. What other factors are associated with hypoglycaemia? • Disease • Endocrine disorders • Addison’s disease • Hypopituitarism • Congenital adrenal hyperplasia • Insulin or OHA abuse

16. …….continued • Disease • Liver and gut disease • Liver failure • Alcohol abuse • Galactosaemia

17. ……continued • Disease • Other disorders • Reye’s syndrome • Malaria • Advanced malignancies • Beckwith-Wiedemann syndrome

18. What is the treatment for hypoglycaemia? • Depends on the severity of hypoglycaemia • In the early stages treated with oral glucose or sucrose - sugar tablets • Lollies • Soft drink and fruit juice • Water with 3tbsp of sugar

19. ……continued • Severe hypoglycaemic events requires treatment with glucagon or IV glucose • 50 or 100ml of 50% glucose followed by continuous infusion of 10% glucose • 0.5 - 1Unit of glucagon given SC, IM, IV for adults. In children, 0.025-0.1mg/kg (max dose 1g)

20. What is glucagon • Glucagon is a polypeptide hormone consisting of 29 amino acids in a single chain. • It is synthesised by genetic engineering from yeast (Saccharomyces cerevisiae) and has the same amino acid sequence as natural human glucagon

21. Function of glucagon • Stimulate an increase in blood concentration of glucose • Major role in maintaining normal concentrations of glucose in blood • Has opposite effect to insulin

22. Physiological pathway 1 • Glucagon stimulates breakdown of glycogen stored in the liver • Glucagon secreted and acts on hepatocytes to activate the enzymes that depolymerise glycogen and release glucose

23. Physiological pathway 2 • Glucagon activates hepatic gluconeogenesis • Non-hexose substrates such as amino acids are converted to glucose

24. Glucagon injections Glucagon can be administered by intramuscular or intravenous injections to achieve rapid increase in blood glucose

25. Glucagon emergency kit • Contain a syringe pre-filled with a liduid and a vial of powder glucagon • Mix immediately before use • Children (<20kg) use 0.5mL (half the syringe) • Adult 1mL (entire syringe) • Inject into large muscle area (eg. buttocks, thigh, arm)

26. Intranasal glucagon spray • Under clinical trial in the Department of Diabetes, Hotel-Dieu Hospital, Paris, France • Glucagon in solution with a surfactant (deoxycholic acid 1% w/v) • Increased plasma glucose levels with a dose-response effect • Hypoglycaemic symptoms were relieved within about 7mins and plasma glucose levels increased by 100% within 25mins • However plasma glucose levels falls within 50 minutes after the dose • Because the effect of intranasal glucagon is transient, oral carbohydrates should be administered after its use in an emergency setting

27. The End